Neutron capture therapy is an attractive method for cancer therapy, specifically the treatment of malignant tumors. The generalized reaction involves capture of a thermalized neutron (usually from a nuclear reactor with special moderators and ports) by an appropriate nucleus having a large neutron capture cross-section. The subsequent decay emits energetic particles (alpha particles) which can kill nearby tumor cells. Since the energetic and cytotoxic alpha particles travel only about one cell diameter in tissue, preferably one may specify the cell type to be destroyed by placing the alpha particle precursors only on or within the tumor cells.
Boron-10 (also designated as .sup.10 B), for example, has such an appropriate nucleus and has particularly advantageous properties for this scheme. The boron-10/thermal neutron capture reaction is as follows (* indicating an unstable intermediate state of the boron nucleus): EQU .sup.10 B+.sup.1 n.fwdarw.[.sup.11 B]*.fwdarw..sup.7 Li(0.87 Mev.)+.sup.4 He(1.52 Mev.)
In order for this therapy to be effective, sufficient .sup.10 B must be localized in a tumor to generate the required density of particles. This level has been variously estimated to be approximately 10-50 .mu.g.sup.10 B/gm tumor. Furthermore, the concentration of .sup.10 B in normal tissue and blood should be limited and preferably less than the concentration in the tumor in order to minimize damage to healthy cells and blood vessels. H. Hatanaka (1986) Boron-Neutron Capture Therapy for Tumors; Nishimura Co., Ltd. p. 1-16.
Large numbers of boron containing compounds have been tested for their ability to satisfy the above criteria. With few exceptions, all have failed as not enough boron has localized in the tumor and the concentration in the blood has been too high for effective neutron capture therapy. Human clinical trials with Na.sub.2 B.sub.12 H.sub.11 SH in Japan have shown some promise, but only for a limited group of brain tumors. Id. 16-26.
Neutron capture therapy would be greatly expanded in usefulness if a generalized method for delivering high concentrations of .sup.10 B to tumors were available. It would further be useful if more .sup.10 B collected in tumor than in the blood.
Recently it has become possible to deliver drugs and other compounds selectively to tumors using liposomes of a particular composition structure. See European Patent Application No. 87311040.7 published Jun. 22, 1988; U.S. Pat. No. 5,019,369 to Presant; and "Liposomes from Biophysics to Therapeutics", M. J. Ostro, Ed., Marcel Dekker, Inc., New York (1987), all of which are incorporated herein by reference.
Incorporation of compounds with higher osmolarity inside the internal space of liposomes than outside, as is necessary for effective neutron capture therapy, depends on incorporating the highest concentration of .sup.10 B possible without substantially altering the liposome's favorable bio-distribution characteristics. Thus, the objective of at least 10 .mu.g .sup.10 B per gram of tumor tissue can be met (assuming use of greater than 90% .sup.10 B enriched material).
Na.sub.2 B.sub.20 H.sub.18 and its hydroxide derivatives are known. See M. F. Hawthorne, R. L. Pilling, and P. M. Garrett, J. Am. Chem. Soc. 87, 4740 (1965). It is known to use boron containing polyphosphonates for the treatment of calcific tumors. See European Patent Application No. 82200784.5 published May 1, 1983. Boronated porphyrin compounds for use in neutron capture therapy are also known. See U.S. Pat. No. 4,959,356 to Miura, U.S. Pat. No. 5,116,980 to Gabel and U.S. Pat. No. 4,466,952 to Hadd.
There is a continuing long felt but unmet need for a method of selectively delivering therapeutic concentrations of .sup.10 B to tumors. There is a similar need for .sup.10 B compositions and delivery vehicles which can be used in boron neutron capture therapy.